Fungicidal compositions and methods of prohibiting the growth thereof

ABSTRACT

BIS (2-CARBAMYLPHENYL) DISULFIDES ARE EFFECTIVE IN CONTROLLING MILDEW FUNGI, ESPECIALLY PULLULARIA PULLULANS AND CAN BE INCORPORATED IN ORGANIC COATING COMPOSITIONS. ABOUT 0.5-1% CONCENTRATION IN PAINT PROVIDES PROTECTION AGAINST MILDEW. THE FUNGICIDAL COMPOUNDS CORRESPOND TO THE STRUCTURAL FORMULA:   1-((2-(R-Y-(CH2)M-NH-CO-)PHENYL)-S-S-),2-(R&#39;&#39;-Z-(CH2)N-   NH-CO-)BENZENE   WHERE R AND R&#39;&#39; ARE SELECTED FROM HYDROGEN AND METHYL, M AND N ARE 2 TO 3 AND Y ARE O OR S.

United lilfW-liieiil iii? 3 i'i'EIZ SQ Int. Cl. C09d 5/14 U.S. Cl.260-22 A 6 Claims ABSTRACT OF THE DISCLOSURE Bis (2-carbamylphenyl)disulfides are effective in controlling mildew fungi, especiallyPullularia pullulans and can be incorporated in organic coatingcompositions. About 0.51% concentration in paint provides protectionagainst mildew. The fungicidal compounds correspond to the structuralformula:

where R and R are selected from hydrogen and methyl, m andnare2or3andYandZareOorS.

CROSS-REFERENCE TO COPENDING APPLICATIONS This application'is a divisionof U.S. patent application Ser. No. 865,977, filed Oct. 13, 1969, nowU.S. Pat. No. 3,663,616, issued May 16, 1972.

BACKGROUND OF THE INVENTION Mildew attack has been a continuing problemin numerous environments where the conditions of humidity andtemperature are conductive to the growth of various microbial life. Mostclimates provide sufiicient environment for growth of fungi on organicnutrient surfaces, such as plants, fibers, and coatings. One area whichhas received great attention is the preventing of mildew fungus growthon exterior organic coatings, especially outside building paints. Thesepaints are applied for protective and decorative purposes over varioussubstrates, usually wood, metal, concrete or ceramics. Painting andrepainting of wood structures in houses and other buildings consumesmanpower and materials in great amounts. The blemishing anddeteriorating effects of various fungi on exterior coatings result inenormous maintenance problems. Because most paints are applied bybrushing or spraying a liquid coating composition onto the surface, themost common method of preventing mildew is to include in the liquid afungicidally effective amount of chemicals which kill the fungiresponsible for the mildew growth.

Numerous attempts been made to increase the resistance of exteriorcoatings to mildew fungi. Inorganic compounds such as zinc oxide orleaded zinc oxide are useful for retarding mildew growth, but thesecomponents detract from moisture resistance on the films. One approachto the problem has been the controlled chalking of the film by additionof anatase titanium dioxide pigment; however,

this caused more rapid erosion of the coating during weathering.

Because moisture is important to mildew growth, the chemical nature ofthe organic coating film is significant. Many hydrophobic coatings, suchas silicones, vinyls, olefins, etc., are not susceptible to mildewgrowth because of this. Such hydrophobic films are usually cured byheating, and are not adapted to maintenance coatings. Most air-dryingpaints do cotain hydrophilic groups, such as carboxyl, hydroxyl, ether,or amine. These paints include the more common alkyd solvent-type,water-emulsified latex, and drying oil types.

Mildew growth on exterior organic coatings is attributed to severalfungi. The relative importance of different species of fungi isclimatically dependent; but, Pullularia species usually account for themajor number of fungus colonies on painted surfaces in the UnitedStates. In warm, moist climates such as the Gulf areas around the 30thparallel, Pullularia species account for about to over of mildew growth.North of the 40th parallel this species amounts to more than half thegrowth. In the warmer moist areas, Alternaria species, Cladosporiumspecies, and Penicillium species are secondary causes of discoloration.In the northern climates Aspergillus species also is a secondary mildewfungus.

A number of other micro-organisms, such as Rhodotorula (yeast), Monilia,Mucor and Botrytis, are minor causes of mildew. An organic surface thatis a nutrient for some fungi may not be a nutrient for others.Generally, a nutrient for other fungi will also support Pullulariagrowth. Alternaria occurrence is higher in latex paints, whereasCladosporium does not thrive on atypical latex film. Rhodotorula isassociated mostly with drying oil paint vehicles and areas protectedfrom weathering (e.g., under caves).

The preferred method for controlling mildew growth on exterior coatingsis to incorporate antifungal compositions into the liquid coatingmaterial before application to the substrate. In order to achieveuniform distribution of the antifungal additives, the mixing should be'performed as an industrial operation, rather than adding the fungicidein the field. For this reason chemical compatibility of the fungicidewith the liquid material is important. Many fungicides lose theirfungicidal activity prior to being applied in a film. This isparticularly significant in latex liquid paints, which are usuallyalkaline. Thus, container storage life is an important criterion forselecting a paint fungicide. While small amounts of biologically activecompounds may prevent deterioration of film-forming materials byanaerobic micro-organisms in a sealed can, the most important functionof paint fungicides is'the prevention of mildew on a nutrient surfaceexposed to ambient air. The weathering environment to which mostexterior coatings are exposed proves to be detrimental to the biologicalactivity of many chemical compounds.

Other chemical and physical properties to be considered for fungicideadditives include animal toxicity, color, solubility (especially inwater) film permeability, volatility, and odor. Mercury compounds, suchas phenyl mercuric phthalate, are effective against some fungi, butharmful to humans and do not prove dependable under field conditions.Dark materials, such as cuprous oxide, cannot be used in light-coloredfilms. Many sulfur-containing compounds, for instance mercaptans, givean unpleasant or noxious odor to the coatings. Nitrogenous J compoundsoften interfere with drying properties of oil paints. If a fungicide istoo water soluble, it may be leached from the film by condensed moistureor precipitation. If the fungicide does not migrate through the coatingfilm, it may remain buried below the paint surface and be ineffective.The mere fact that a chemical compound is known for its activity againstfungi does not mean that it will be successful for inhibiting fungalgrowth on exterior surface for long periods of time.

Several organic compounds have gained acceptance as exterior paintfungicides. Captan(N-trichloromethylmercapto-4-cyclohexene-1,2-carboximide) has been usedfor this purpose, and is effective against Pullularia and other fungi.Trans-1,2-bis(n-propylsulfenyl) ethylene (U.S. Pat. 3,199,990) is highlyeffective in alkyl and oil paints. 2,3,5,6-tetrachloro-4-(methylsulfonyl) pyridine is used in many latex paintsas a fungicide.

Deterioration and discoloration of exterior films by microbial growthare discussed by Rothwell in the F.P.V.P.C. Ofiicial Digest, April 1958,pp. 368-376. Several fungi, yeast and bacteria species are known tocause mildew growth on exterior paints, but Pullularia has been reportedas the major cause in over 95% of reported cases.

BRIEF SUMMARY OF THE INVENTION Good activity against fungi has beendiscovered for certain substituted bis(2-alkylcarbamylphenyl) disulfidescorresponding to the structure formula where R and R' are selectedindependently from hydrogen and methyl, m and n are whole integers from2-3, and Y and Z are or S.

These compounds exhibit good fungicidal properties. In serial dilutionexperiments, in vitro activity was observed as low as 8 p.p.m., andenvironmental testing of organic films containing these compounds haveindicated their usefulness in inhibiting growth of important fungi foundin exterior paints.

DESCRIPTION The disulfide compounds used in the practice of thisinvention can be synthesized by reacting the required amount of theappropriate amine with 2,2-dithiodibenzoyl halide. The followingexamples are representative of the invention, but the inventive conceptis not limited to such examples. Units are expressed as parts by weightunless otherwise stated.

EXAMPLE 1 propylcarbamyl) phenyl] disulfide, having a melting point of126-127 C. The structure was confirmed by nuclear magnetic resonancestudies.

Analysis.Calculated for C H N O S (percent): C, 58.90; H, 6.29; N, 6.25;S, 14.29. Found (percent): C, 59.34; H, 6.37; N, 6.08; 5, 14.52.

4 EXAMPLE 2 A solution of 206 parts of 2,2-dithiodibenzoyl chloride in3000 parts of warm p-dioxane was added slowly with stirring to asolution of 187.5 parts of S-amine-l-propanol in 1000 parts of p-dioxaneat a temperature of 30-40". The thick slurry was heated at 50-60 C. fortwo hours and cooled. The precipitated solid was filtered off, stirredin 1000 parts of Water twice, filtered off and dried to give 184 partsof crude bis[2-(3-hydroxypropylcarbamyl) phenyl] disulfide.Recrystallization from ethanol gave the pure compound, melting point170-171 C.

Analysis-Calculated for C H N O S (percent): C, 57.12; H, 5.75; N, 6.66;S, 15.25. Found (percent): C, 57.19; H, 5.84; N, 6.69; S, 15.53.

The MIC against Pullularia pullulans and Penicillium oxalicum was 62ppm.

EXAMPLE 3 Solid 2,2'-dithiodibenzoyl chloride (206 parts) was addedportionwise with stirring at 25-30 to a solution of 2-aminoethanol (146parts) in dioxane (1000 parts). The mixture was stirred at roomtemperature for one hour, allowed to stand overnight, and theprecipitated solid was filtered off and slurried in water (1000 parts).The solid was filtered off and recrystallized from ethanol to givebis[2-(2-hydroxyethylcarbamyl) phenyl] disulfide, M.P. 182-183 in 62%theoretical yield. Reported M.P. 184. [H. Bushagen, Chem. Berichte, 99,2566 (1966)].

The compound exhibited good activity against Pul- Iularia pullulans.

EXAMPLE 4 Bis[2-(Z-methoxyethylcarbamyl) phenyl] disulfide was preparedin a similar way to the preceding example 3 by reacting2,2'-dithiodibenzoyl chloride with Z-methoxyethylamine. The purecompound melted at 158.5- 159.5 C.

Analysis.-Calculated for C H N O S (percent): C, 57.12; H, 5.75; N,6.66; 8, 15.25. Found (percent): C, 57.10; H, 5.56; N, 6.55; S, 15.12.

The product was active against Pullularia pullulans and and Penicillz'umoxalz'cum.

EXAMPLE 5 A solution of 40.5 parts of 2,2'-dithiodibenzoyl chloride in300 parts of warm dioxane, was added slowly with stirring at 25-30 to asolution of parts of dioxane containing 25 parts of3-methylthiopropylamine and 25 parts of triethylamine. The mixture wasthen heated to 5060 C. for two hours and cooled. The precipitated solidwas filtered off, stirred in 500 parts of water to dissolvetriethylamine hydrochloride, filtered off, washed with water and driedto give 41 parts of crude bis[2-(3-methylthi0- propylcarbamyl) phenyl]disulfide. The pure product was obtained by recrystallization fromethanol.

Analysis.-Calculated for C H N O S (percent): C, 54.96; H, 5.87; N,5.83; 5, 26.68. Found (percent): C, 54.98; H, 5.71; N, 5.70; S, 26.46.

Comparative tests of the substituted bis(2-alky1carbamylphenyl)disulfides in vitro have established their usefulness in controllinggrowth of fungi in organic nutrient media. These tests showed that theminimum in hibitory concentration of the compounds against Pullulariapullulans and Penicillium oxalicum species was in the range of 8-1250PPM. They were performed as follows: The samples were dissolved in smallquantities of ethanol or acetone, made to volume with sterile Sabouraudliquid medium, inoculated with fungi and incubated at 25 C. for sevendays. The lowest concentration (in parts per million) which inhibitedthe growth of the test fungi was recorded.

EXAMPLE 6 Bis[2 (3-hydroxypropylcarbamyl) phenyl] disulfide wasincorporated at 1% concentration in latex paint containing the followingcomponents:

Parts Acrylic resin latex (Rohm and Haas AC-388, 50%

solids) 410 Pentaerythritol phthalate resin (Aroplaz 1271) 50 Alkyleneglycol 70 Hydroxyethyl cellulose l Trialkyl phgsphateplasticizei;M'e'tiliiaphthanates 2 Anionic surfactants and emulsifiers 29 Titaniumdioxide pigments 305 Alkaline earth silicate pigment 150 Alkaline earthcarbonate pigment 45 Defoamer 2 Ammonium hydroxide 2 and Water 169 Thislatex paint contained about 68 percent solids.

A normal brush coat was applied to both sides of a filter paper squarein three replicates. Another batch of paint containing allaforementioned ingredientsin the same proportion-but no fungicidaldisulfide was also prepared in exactly the same manner. A normal brushcoat of this paint was then applied to both sides of filter papersquares in the three replicates which provided the control specimens.All the squares of the coated paper (sample and control) were then laidon agar plates in a sterile environment, inoculated with Dullulariapullulans and incubated at 28 C., 96% relative humidity. At 7, l4 and21-day periods, they were examined for fungi growth. The samplescontaining disulfide were found completely free of fungi growth, whereasthe control specimens exhibited light, moderate and heavy growth after7, 14 and 21 days, respectively.

EXAMPLE 7 A normal brush coat of an alkyd paint conta ning bis[2-(3-methoxypropylcarbamy) phenyl] disulfide at 1% concentration wasapplied to both sides of filter paper squares in three replicates. Thispaint included the following components:

The liquid alkyd paint contained about 87 weight percent solids.

Another batch-of paint containing no fungicidal disulfide was preparedexactly as described above. A normal brush coat of the paint was appliedto both sides of filter paper squares in three replicates providing thecontrol specimens.

The squares of the coated paper (sample and control) were then laid onagar plates in a sterile environment, inoculated with Pullulariapullulans and incubated at 28 C.

and 96% relative humidity, and inspected at 7, 14 and 21-day intervals.The samples containing the fungicide were found completely free of fungigrowth, whereas the control specimens showed light growth after 21 daysof exposure.

A more severe test to evaluate fungicides for paints is an acceleratedweathering test, which is helpful in anticipating field performance (P.A. Wolf et al., Amer. Chem. Soc. Div. of Coatings and Plastics, 25, 23(1965)). This method was used in testing the novel disulfides asillustrated by Examples 8 and 9.

EXAMPLE 8 A 0.5% concentration of bis[2-(3-hydroxypropylcarbamyl)phenyl] disulfide in latex paint was prepared as described in Example 6.Latex paint containing no disulfide was prepared in exactly the sameway. The two paints were applied in an appropriate manner, weathered foran appropriate period of time and subjected to mildew attack in amodified tropical chamber. The additive provided a significant degree ofprotection.

EXAMPLE 9 The aforementioned disulfide was incorporated at 1%concentration into the alkyd paint described in Example 6 and evaluatedas in Example 8. The disulfide provided a significant degree ofprotection over the control sample.

The fungicidal disulfide compounds may be used with a wide variety ofoils, resin, solvents, pigments and coating additives in formulatingorganic film-forming compositions having mildew resistance. The morecommon types of exterior coatings for which these compounds are usefulas fungicides include the drying oils, alkyds and latextype paints. Thefilm-forming vehicles include the triglyceride esters of unsaturatedfatty acids such as linseed oil or soya oil; esters of polycarboxylicacids with polyols, such as reaction products of phthalic anhydride withglycerol or pentaerythritol; oil-modified alkyds; modified phenolicresins, such as aldehyde condensations; melamine resins; syntheticelastomeric latexes; homopolymers or copolymers of olefinicallyunsaturated compounds, including vinyl acetates and acrylic resins;urethane resins; ether resins and numerous othei conventional coatingvehicles. Typical pigments which can be combined in exterior paintscomprise titanium dioxide, alkaline earth carbonates and silicates,bentonite, mica, metal oxides, carbon, etc. Solvents and co-solvents areused conventionally in both organic-thinned or water thinned coatingcompositions, for instance, mineral spirits, polyols, benzoids, etc.Numerous additives can be incorporated in the antifungal paints forsuppressing foam, for plasticizing the dried films, for emulsifyinglatexes, or for accelerating the film cure.

While the antifungal additive is usually incorporated directly into acoating to be applied as a top coat, some organic coatings, can beadequately protected by using the antifungal additive in a primer orintermediate coat. Migration into an adjacent layer from a substratecontaining a fungicide can be an effective means for controlling mildewin some applications. A relatively higher local concentration offungicidal agent may be necessary under such conditions. Directapplication of the fungicide with an inert carrier over the organicnutrient surface may be used to protect against fungus growth, but thismethod may not be desirable for exterior weathered surfaces due toerosion. Some interior surfaces in food processing rooms, such asbakeries, breweries, meat packing plants, etc., also suffer from mildewgrowth due to extreme conditions of humidity or temperature. Here theweathering effect is not such an important factor, but the use of afungicide is desirable.

The preferred concentrations of the disulfides in the dry coating filmsis from the minimum inhibitory amount to about 2 percent by Weight.Greater amounts may be used, but no particular benefit is gained fromusing concentrations much higher than the minimum fungicidally effectiveamount of these compounds.

While the invention has been described by specific examples, there is nointent to limit the inventive concept except as set forth in thefollowing claim.

What is claimed is:

1. A mildew-resistant organic coating composition containing a vehicleand a fungicidally effective amount of at least one compound having thestructure:

pound selected from the class consisting of bis[2-(3-me- 3thoxypropylcarbamyl) phenyl] disulfide and bis[2-(3-hydroxypropylcarbamyl) phenyl] disulfide.

5. A process for controlling mildew growth on a substrate whichcomprises coating said substrate with a liquid organic coatingcomposition containing a vehicle and a fungicidally effective amount ofat least one compound having the structure:

where R and R are selected independently from hydrogen and methyl andwhere Y and Z are 0 or S.

6. A process for controlling mildew growth on a substrate whichcomprises coating said substrate with a liquid organic coatingcomposition containing a vehicle and a fungicidally effective amount ofat least one compound having the structure:

CONH(CHz)g-YCH; --s-s-4( C H3Z(CH1)2NHC 0 where Y and Z are selectedindependently from O and 5.

References Cited UNITED STATES PATENTS 3,192,057 6/1965 Hines et al.106-15 AF 3,266,913 8/1966 Hardy et al 106-15 AF 3,595,817 7/1971 Deinet260-22 R 3,642,501 2/1972 Minieri 106-15 AF DONALD E. CZAJA, PrimaryExaminer R. W. GRIFFIN, Assistant Examiner US. Cl. X.R.

106-15 AF; 117-161 K; 260-23 AR, 29.2 E, 29.6 MQ; 424-324

